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Methylation at 5HTT Mediates the Impact of Child Sex Abuse on Women's Antisocial Behavior: An Examination of the Iowa Adoptee Sample.

Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA

Department of Psychology (S.R.H.B.) and Center for Family Research (G.H.B.), University of Georgia, Athens, Georgia; Department of Psychiatry (A.A.T.), Washington University, St. Louis, Missouri; Department of Neurology and Psychiatry (T.D.G.), St. Louis University School of Medicine, St. Louis, Missouri; and the Department of Psychiatry (R.A.P.), Neuroscience and Genetics Programs, University of Iowa, Iowa City, Iowa.

Objective: To examine epigenetic processes linking childhood sex abuse to symptoms of antisocial personality disorder (ASPD) in adulthood and to investigate the possibility that the link between childhood sex abuse and deoxyribonucleic acid methylation at the 5HTT promoter might represent a pathway of long-term impact on symptoms of ASPD. Method: Deoxyribonucleic acid was prepared from lymphoblast cell lines derived from 155 female participants in the latest wave of the Iowa Adoptee Study. Methylation at 71 CpG residues was determined by quantitative mass spectroscopy, and the resulting values were averaged to produce an average CpG ratio for each participant. Simple associations and path analyses within an Mplus framework were examined to characterize the relationships among childhood sex abuse, overall level of methylation among women, and subsequent antisocial behavior in adulthood. Direct effects of biological parent psychopathology and 5HTT genotype were controlled. Results: Replicating prior work, we found that a significant effect of childhood sex abuse on methylation of the 5HTT promoter region emerged for women. In addition, a significant effect of methylation at 5HTT on symptoms of ASPD emerged. Conclusions: Child sex abuse may create long-lasting changes in methylation of the promoter region of 5HTT in women. Furthermore, hypermethylation may be one mechanism linking childhood sex abuse to changes in risk for adult antisocial behavior in women. Better understanding of the methylome may prove critical in understanding the role of childhood environments on long-term psychiatric sequelae.